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See detailLIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort
Usnich, Tatiana; Vollstedt, Eva-Juliane; Schell, Nathalie et al

in Frontiers in Neurology (2021), 12

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 ( LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2 -linked PD is clinically indistinguishable ... [more ▼]

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 ( LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2 -linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data. Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2 -linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants. Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn \&Yahr, and Schwab \& England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021). Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2 -linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration: ClinicalTrials.gov , NCT04214509. [less ▲]

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See detailTUMOUR-ASSOCIATED MICROGLIA/MACROPHAGE HETEROGENEITY IN GLIOBLASTOMA
Pires Afonso, Yolanda Sofia UL

Doctoral thesis (2021)

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors ... [more ▼]

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors promoting the recruitment and infiltration of cellular players to the local tumour microenvironment. Tumour-associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment in GBM playing important roles along tumour development. Along GBM progression, these cells are supposed to be geared towards a tumour-supportive phenotype, therefore TAMs are pursued as key targets for the development of novel strategies aimed at re-educating them towards anti-tumour phenotypes. However, it is yet unclear how these immune suppressive properties are acquired and whether TAM subsets may phenotypically and functionally differently contribute to tumour development. Hence, the main goal of the present PhD project was to elucidate TAM diversity under defined temporal and spatial settings in GBM. Taking advantage of the GBM GL261 syngeneic and patient-derived orthotopic xenograft mouse models, we comprehensively studied the cellular and transcriptional heterogeneity of TAMs by combining single-cell RNA-sequencing, multicolour flow cytometry, immunohistological and functional analyses. We demonstrated that, as observed in patients, the myeloid compartment is the most affected and heterogeneous stromal compartment, with microglia and macrophage-like cells acquiring key transcriptional differences and rapidly adapting along GBM progression. Specifically, we uncovered that TAM transcriptional programmes converge over time, suggesting a context-dependent symbiosis mechanism characterized by decreased antigen-presenting cell signatures at late tumour stages. In the absence of Acod1/Irg1, a key gene involved in the metabolic reprogramming of macrophages towards an anti-inflammatory phenotype, we detected higher TAM diversity in the TME displaying increased immunogenicity and correlating with increased lymphocytic recruitment to the tumour site. Additionally, we uncovered that TAMs exhibit niche-specific functional adaptations in the tumour microenvironment, with microglia in the invasive landscapes displaying higher immune reactive profiles when compared to the corresponding cells in the angiogenic tumour phenotypes. Taken together, our data provide insights into the spatial and molecular heterogeneity of TAMs dynamically adapting along tumour progression or across specific tumour sites and revealing potential reactive anti-tumorigenic cell subsets that may be harnessed for therapeutic intervention in GBM. [less ▲]

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See detailDevelopment and Application of Liquid Chromatographic Retention Time Indices in HRMS-Based Suspect and Nontarget Screening
Aalizadeh, Reza; Alygizakis, Nikiforos A.; Schymanski, Emma UL et al

in Analytical Chemistry (2021), 93(33), 11601--11611

There is an increasing need for comparable and harmonized retention times (tR) in liquid chromatography (LC) among different laboratories, to provide supplementary evidence for the identity of compounds ... [more ▼]

There is an increasing need for comparable and harmonized retention times (tR) in liquid chromatography (LC) among different laboratories, to provide supplementary evidence for the identity of compounds in high-resolution mass spectrometry (HRMS)-based suspect and nontarget screening investigations. In this study, a rigorously tested, flexible, and less system-dependent unified retention time index (RTI) approach for LC is presented, based on the calibration of the elution pattern. Two sets of 18 calibrants were selected for each of ESI+ and ESI-based on the maximum overlap with the retention times and chemical similarity indices from a total set of 2123 compounds. The resulting calibration set, with RTI set to range between 1 and 1000, was proposed as the most appropriate RTI system after rigorous evaluation, coordinated by the NORMAN network. The validation of the proposed RTI system was done externally on different instrumentation and LC conditions. The RTI can also be used to check the reproducibility and quality of LC conditions. Two quantitative structure−retention relationship (QSRR)-based models were built based on the developed RTI systems, which assist in the removal of false-positive annotations. The applicability domains of the QSRR models allowed completing the identification process with higher confidence for substances within the domain, while indicating those substances for which results should be treated with caution. The proposed RTI system was used to improve confidence in suspect and nontarget screening and increase the comparability between laboratories as demonstrated for two examples. All RTI-related calculations can be performed online at http://rti.chem.uoa.gr/. [less ▲]

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See detailPodcast Café du Savoir. Episode 1: PITT– Programme for Innovative Teaching & Training
Baumann, Isabell Eva UL; Bissen, Manuel; Harion, Dominic UL et al

Speeches/Talks (2021)

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See detailVisualisation Techniques for Consent: Finding Common Ground in Comic Art with Indigenous Populations
Botes, Wilhelmina Maria UL; Rossi, Arianna UL

in 2021 IEEE European Symposium on Security and Privacy Workshops (EuroS&PW) (2021)

With emerging technologies such as genome research and the digitization of health records comes the need for new models of informed consent. In this climate of innovation people are often prone to explore ... [more ▼]

With emerging technologies such as genome research and the digitization of health records comes the need for new models of informed consent. In this climate of innovation people are often prone to explore the latest technological advancement as possible solutions, including for informed consent. In this paper, we present the design and evaluation of a so-called low-tech informed consent solution that was designed specifically for the informational and cultural needs of a vulnerable indigenous population, i.e., the San of South Africa. This low-tech solution took the form of a comic and, although it could enhance understanding and identification, the costs and labour intensity of comic design and the deriving limitations on its scalability should be critically considered in the light of a digitised and more standardized solution. [less ▲]

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See detailChemical vapor deposition of CoFe2O4 micropillar arrays with enhanced magnetic properties
Aspe, B.; Malyeyev, Artem UL; Vakilinejad, A. et al

in Journal of Alloys and Compounds (2021), 890

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See detailDon’t Put the Cart Before the Horse – Effective Incident Handling Under GDPR and NIS Directive
Schmitz, Sandra UL; Schiffner, Stefan UL

in Friedewald, Michael; Schiffner, Stefan; Krenn, Stephan (Eds.) Privacy and Identity Management (2021)

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See detailTagungsbericht: Rethinking the Histories and Legacies of Industrial Cities
Derian, Maxime UL; van de Maele, Jens UL

in Moderne Stadtgeschichte (2021), (1), 145-150

The history of (Western) European industrial cities is often told as a tragic tale of rise and decline: from rapid industrialisation in the late 19th century and economic prosperity during the Trente ... [more ▼]

The history of (Western) European industrial cities is often told as a tragic tale of rise and decline: from rapid industrialisation in the late 19th century and economic prosperity during the Trente glorieuses to the structural changes of the late 1970s and the subsequent deindustrialisation of the 1980s and 1990s – decades in which most mines and steelworks closed down, unemployment rates went up, new social problems emerged, workers’ identities eroded, and once prosperous urban centres became faced with shrinking populations and empty stores in their shopping streets. Finally, since the 2000s, former industrial towns have tried to reinvent themselves as creative and cultural centres. If we take a closer look, however, we can see that the socio-economic, demographic and cultural transitions were more complex than suggested by a simple rise-and-decline narrative. [less ▲]

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See detailTowards Exploring the Limitations of Active Learning: An Empirical Study
Hu, Qiang UL; Guo, Yuejun UL; Cordy, Maxime UL et al

in The 36th IEEE/ACM International Conference on Automated Software Engineering. (2021)

Deep neural networks (DNNs) are being increasingly deployed as integral parts of software systems. However, due to the complex interconnections among hidden layers and massive hyperparameters, DNNs ... [more ▼]

Deep neural networks (DNNs) are being increasingly deployed as integral parts of software systems. However, due to the complex interconnections among hidden layers and massive hyperparameters, DNNs require being trained using a large number of labeled inputs, which calls for extensive human effort for collecting and labeling data. Spontaneously, to alleviate this growing demand, a surge of state-of-the-art studies comes up with different metrics to select a small yet informative dataset for the model training. These research works have demonstrated that DNN models can achieve competitive performance using a carefully selected small set of data. However, the literature lacks proper investigation of the limitations of data selection metrics, which is crucial to apply them in practice. In this paper, we fill this gap and conduct an extensive empirical study to explore the limits of selection metrics. Our study involves 15 selection metrics evaluated over 5 datasets (2 image classification tasks and 3 text classification tasks), 10 DNN architectures, and 20 labeling budgets (ratio of training data being labeled). Our findings reveal that, while selection metrics are usually effective in producing accurate models, they may induce a loss of model robustness (against adversarial examples) and resilience to compression. Overall, we demonstrate the existence of a trade-off between labeling effort and different model qualities. This paves the way for future research in devising selection metrics considering multiple quality criteria. [less ▲]

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See detailPolicy Brief – Le Capital Social : les Facilitateurs et les Obstacles à l’Intégration des Jeunes Migrants au Luxembourg
Vysotskaya, Volha UL; Oliveira, José UL; Nienaber, Birte UL

Report (2021)

The Policy Brief opposite is based on the results of the SOCAMI project, which was drawn up on the basis of secondary analysis of European and national data concerning the socio-professional integration ... [more ▼]

The Policy Brief opposite is based on the results of the SOCAMI project, which was drawn up on the basis of secondary analysis of European and national data concerning the socio-professional integration of young migrants, as well as qualitative data collected as part of this study. Indeed, twelve biographical interviews were conducted by the researchers involved in the project with young migrants who had been living in Luxembourg for more than five years. This analysis was completed by eight expert interviews with representatives of organisations working with young people and/or migrants in various fields. These different analyses made it possible, on the one hand, to develop relevant indicators to measure the acquisition of social capital by young migrants and, on the other hand, to identify the structural obstacles to the social integration of this group. Based on these results, this document makes a number of recommendations for governmental and non-governmental organisations working with young people and/or migrants. [less ▲]

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See detailSNR-Based GNSS-R for Coastal Sea-Level Altimetry
Tabibi, Sajad UL; Sauveur, Renaldo UL; Guerrier, Kelly et al

in Geosciences (2021), 11(9 391),

Geodetic Global Navigation Satellite System reflectometry (GNSS-R) uses ground-based signals of opportunity to retrieve sea levels at an intermediate spatial scale. Geodetic GNSS-R is based on the ... [more ▼]

Geodetic Global Navigation Satellite System reflectometry (GNSS-R) uses ground-based signals of opportunity to retrieve sea levels at an intermediate spatial scale. Geodetic GNSS-R is based on the simultaneous reception of Line-of-Sight (LoS) and its coherent GNSS sea surface reflection (non-LOS) signals. The scope of this paper is to present geodetic GNSS-R applied to sea level altimetry. Signal-to-Noise Ratio (SNR) measurements from a Commercial Off-The-Shelf (COTS) geodetic-quality GNSS station at the Haiti Coast Guard Base in Port-au-Prince is used to retrieve sea levels in the International Terrestrial Reference Frame 2014 (ITRF2014). The GNSS-R sea levels are compared with those of the OTT Radar Level Sensor (RLS) installed vertically below the GNSS antenna. The Root-Mean-Square Error (RMSE) between the geodetic GNSS-R sea levels and OTT RLS records is 3.43 cm, with a correlation of 0.96. In addition, the complex differences between the OTT RLS records and 15-min GNSS-R sea levels using Global Positioning System (GPS) and Globalnaya Navigazionnaya Sputnikovaya Sistema (or Global Navigation Satellite System; GLONASS) signals for all the eight major tidal constituents are in mm-level agreement. Therefore, geodetic GNSS-R can be used as a complementary approach to the conventional method for sea level studies in a stable terrestrial reference frame. [less ▲]

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See detailElectricity Spot Market Design 2030-2050
Novirdoust, Amir Ashour; Bichler, Martin; Bojung, Caroline UL et al

Report (2021)

Driven by the climate conference in Paris in December 2015 countries worldwide are confronted with the question of how to shape their power system and how to establish alternative technologies to reduce ... [more ▼]

Driven by the climate conference in Paris in December 2015 countries worldwide are confronted with the question of how to shape their power system and how to establish alternative technologies to reduce harmful CO2 emissions. The German government plans that even before the year 2050, all electricity generated and consumed in Germany should be greenhouse gas neutral [1]. To successfully integrate renewable energies, a future energy system must be able to handle the intermittent nature of renewable energy sources such as wind and solar. One important means to address such electricity production variability is demand-side flexibility. Here, industry plays a major role in responding to variable electricity supply with adequate flexibility. This is where the Kopernikus project SynErgie comes in with more than 80 project partners from academia, industry, governmental, and non-governmental organizations as well as energy suppliers and network operators. The Kopernikus project SynErgie investigates how to best leverage demand-side flexibility in the German industry. The current electricity market design in Germany is not well suited to deal with increasing levels of re- newable energy, and it does not embrace demand-side flexibility. Almost 6 GW of curtailed power in 2019 provide evidence that changes are needed with respect to the rules governing electricity markets. These rules were designed at a time when electricity generation was concentrated on a few large and dispatchable conventional power plants and demand was considered inelastic. The SynErgie Cluster IV investigates how a future-proof electricity market design should be organized. The corresponding Work Package IV.3.1 more specifically deals with analyzing and designing allocation and pricing rules on electricity spot markets. The resulting design must be well suited to accommodate demand-side flexibility and address the intermittent nature of important renewable energy sources. This whitepaper is the result of a fruitful collaboration among the partners involved in SynErgie Cluster IV which include Germany’s leading research organizations and practitioners in the field. The collaboration led to an expert workshop in October 2020 with participation from a number of international energy market experts such as Mette Bjørndal (NHH), Endre Bjørndal (NHH), Peter Cramton (University of Maryland and University of Cologne), and Raphael Heffron (University of Dundee). The whitepaper details the key recommendations from this workshop. In particular, the whitepaper recommends a move to a locational, marginal price-based system together with new bidding formats allowing to better express flexibility. We argue in favor of a one-step introduction of locational, marginal prices instead of repeatedly splitting existing zones. Frequent zone splitting involves recurring political debates as well as short- and long-run instabilities affecting the basis for financial con- tracts, for example. Importantly, the definition of stable prize zones is very challenging with increasing levels of distributed and renewable energy sources. The recommendation is the outcome of an intense debate about advantages and downsides of different policy alternatives. However, such a transition to locational, marginal prices is not without challenges, and it is a call to arms for the research community, policymak- ers, and practitioners to develop concepts on how to best facilitate the transition and ensure a reliable and efficient electricity market of the future. We’d like to thank all the project partners and are grateful for the financial support from the Federal Ministry of Education and Research as well as the Project Management Jülich. Hans Ulrich Buhl (Cluster Lead) Martin Bichler (Work Package Lead) [less ▲]

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See detailRenewable electricity business models in a post feed-in tariff era
Rövekamp, Patrick; Schöpf, Michael; Wagon, Felix et al

in Energy (2021), 216

To expand intermittent renewable electricity sources (RESs), worldwide energy policy makers have introduced fixed feed-in tariffs (FITs). However, FITs typically expire after a limited time period. Due to ... [more ▼]

To expand intermittent renewable electricity sources (RESs), worldwide energy policy makers have introduced fixed feed-in tariffs (FITs). However, FITs typically expire after a limited time period. Due to the intermittent electricity supply of RES, market distortions, and insufficient flexibility options, exclusive participation in wholesale electricity markets might not be a viable business model for RES that no longer receive a FIT. Thus, it remains unclear which RES business models (RBMs) ensure a viable operation of RES in the post FIT era. To close this research gap, we present a typology encompassing five RBM archetypes: wholesale electricity market (1), physical power purchase agreements (2), nonphysical power purchase agreements (3), self-consumption (4), and on-site power-2-X (5). The typology includes three additional service layers, which may enhance the profitability of RBM archetypes by opening up additional revenue streams: infrastructure services (1), electricity storage services (2), and ancillary services (3). We highlight the need for new approaches to quantify the viability of RBM archetypes and services layers under different regulatory, technological, and market conditions. To prevent the imminent decommissioning of existing RESs, policy makers must shape the next era of the energy transition, weighting the implications of market-based and intervention-based energy policy approaches. [less ▲]

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See detailBlockchain Won’t Kill the Banks: Why Disintermediation Doesn’t Work in International Trade Finance
Fridgen, Gilbert UL; Radszuwill, Sven; Schweizer, André et al

in Communications of the Association for Information Systems (2021), 49

In the financial services industry, many people assume blockchain to have significant impacts. From research and practice, we observe two main paradigms of how organizations interact with blockchain ... [more ▼]

In the financial services industry, many people assume blockchain to have significant impacts. From research and practice, we observe two main paradigms of how organizations interact with blockchain. First, organizations use blockchain to optimize existing processes (blockchain-based business process optimization (BPO)). Second, organizations use blockchain to disrupt existing processes, foster disintermediation, and enable disruptive business models (blockchain-based business process disruption (BPD)). However, we lack scientific research that evaluates its de facto potential. We bridge this gap by following a design science research approach to design blockchain-based business process re-engineering (BPRE) for a letter of credit that combines the advantages of BPO and BPD. We conduct three design cycles and develop three artefacts: a BPO, a BPD, and a BPRE approach. Our BPRE approach combines the advantages of partial disintermediation (i.e., increased efficiency and transparency) with the advantages of intermediaries (i.e., process flexibility, liquidity provision, and dispute mediation). [less ▲]

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See detailDiagnostics and correction of batch effects in large-scale proteomic studies: a tutorial.
Čuklina, Jelena; Lee, Chloe H.; Williams, Evan UL et al

in Molecular systems biology (2021), 17(8), 10240

Advancements in mass spectrometry-based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much-needed statistical power, handling them introduces ... [more ▼]

Advancements in mass spectrometry-based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much-needed statistical power, handling them introduces technical variability known as batch effects. Here, we present a step-by-step protocol for the assessment, normalization, and batch correction of proteomic data. We review established methodologies from related fields and describe solutions specific to proteomic challenges, such as ion intensity drift and missing values in quantitative feature matrices. Finally, we compile a set of techniques that enable control of batch effect adjustment quality. We provide an R package, "proBatch", containing functions required for each step of the protocol. We demonstrate the utility of this methodology on five proteomic datasets each encompassing hundreds of samples and consisting of multiple experimental designs. In conclusion, we provide guidelines and tools to make the extraction of true biological signal from large proteomic studies more robust and transparent, ultimately facilitating reliable and reproducible research in clinical proteomics and systems biology. [less ▲]

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See detailNanoscale interfacial engineering enables highly stable and efficient perovskite photovoltaics
Krishna, Anurag; Zhang, Hong; Zhou, Zhiwen et al

in Energy and Environmental Science (2021)

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See detailA platform for experimental precision medicine: The extended BXD mouse family.
Ashbrook, David G.; Arends, Danny; Prins, Pjotr et al

in Cell systems (2021), 12(3), 235-2479

The challenge of precision medicine is to model complex interactions among DNA variants, phenotypes, development, environments, and treatments. We address this challenge by expanding the BXD family of ... [more ▼]

The challenge of precision medicine is to model complex interactions among DNA variants, phenotypes, development, environments, and treatments. We address this challenge by expanding the BXD family of mice to 140 fully isogenic strains, creating a uniquely powerful model for precision medicine. This family segregates for 6 million common DNA variants-a level that exceeds many human populations. Because each member can be replicated, heritable traits can be mapped with high power and precision. Current BXD phenomes are unsurpassed in coverage and include much omics data and thousands of quantitative traits. BXDs can be extended by a single-generation cross to as many as 19,460 isogenic F1 progeny, and this extended BXD family is an effective platform for testing causal modeling and for predictive validation. BXDs are a unique core resource for the field of experimental precision medicine. [less ▲]

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See detailThe Long-Term Effect of Research Grants on the Scientific Output of University Professors
Hussinger, Katrin UL; Carvalho, J.N.

E-print/Working paper (2021)

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See detailBildung für nachhaltige Entwicklung als Kompetenzorientierung
Andersen, Katja Natalie UL

in KiTa aktuell HRS - Fachzeitschrift für Leitungen, Fachkräfte und Träger der Kindertagesbetreuung (2021), 29(9), 197

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See detailRapport final Projet 2020: Le capital social dans l'intégration des jeunes migrants au Luxembourg
Vysotskaya, Volha UL; Oliveira, José UL; Nienaber, Birte UL

Report (2021)

The SOCAMI project focuses on the importance of social ties in the integration pathways of young migrants from third countries in Luxembourg. Youth is a period rich in learning where social identities and ... [more ▼]

The SOCAMI project focuses on the importance of social ties in the integration pathways of young migrants from third countries in Luxembourg. Youth is a period rich in learning where social identities and feelings of belonging to a social group are developed. In this sense, the analysis of the role of social ties in the integration of young migrants is essential. In particular, the ties that young migrants establish with residents of their host country may endure in the future and should therefore be considered relevant in the formation of their social relationships. However, young migrants often find themselves in vulnerable situations linked to job insecurity or, more broadly, marginalisation within the host society. Thus, it is mainly the relationships fostered by youth organisations, governmental or non-governmental, formal or informal, that play a central role in the preparation of young migrants for adult life. The overall aim of this study is to understand, investigate, explain and scientifically formulate the role of social capital in the integration of young migrants residing in Luxembourg. [less ▲]

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